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International Journal of Molecular... Aug 2021Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation.... (Review)
Review
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future.
Topics: Animals; Dental Pulp; Guided Tissue Regeneration, Periodontal; Humans; Mesenchymal Stem Cells; Regeneration; Retrospective Studies; Root Canal Therapy; Stem Cells; Tissue Engineering
PubMed: 34445703
DOI: 10.3390/ijms22168991 -
Indian Journal of Anaesthesia Sep 2016Statistical methods involved in carrying out a study include planning, designing, collecting data, analysing, drawing meaningful interpretation and reporting of the... (Review)
Review
Statistical methods involved in carrying out a study include planning, designing, collecting data, analysing, drawing meaningful interpretation and reporting of the research findings. The statistical analysis gives meaning to the meaningless numbers, thereby breathing life into a lifeless data. The results and inferences are precise only if proper statistical tests are used. This article will try to acquaint the reader with the basic research tools that are utilised while conducting various studies. The article covers a brief outline of the variables, an understanding of quantitative and qualitative variables and the measures of central tendency. An idea of the sample size estimation, power analysis and the statistical errors is given. Finally, there is a summary of parametric and non-parametric tests used for data analysis.
PubMed: 27729694
DOI: 10.4103/0019-5049.190623 -
Cellular & Molecular Immunology Jan 2022The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of... (Review)
Review
The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.
Topics: CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cross-Priming; Dendritic Cells; Humans; Neoplasms
PubMed: 34480145
DOI: 10.1038/s41423-021-00741-5 -
Advanced Science (Weinheim,... Sep 2023Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in...
Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin-dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin-resistant cells and tissues due to the loss of N6-methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient-derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl-CoA synthetase long-chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron-dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin-resistant CRC.
Topics: Humans; CDC2 Protein Kinase; Colorectal Neoplasms; Ferroptosis; Oxaliplatin; Proteolysis
PubMed: 37428466
DOI: 10.1002/advs.202301088 -
Current Opinion in Lipidology Aug 2019Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly... (Review)
Review
PURPOSE OF REVIEW
Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as 'bystanders' for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases.
RECENT FINDINGS
The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death.
SUMMARY
For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.
Topics: Animals; Atherosclerosis; Humans; Hypertriglyceridemia; Risk Factors
PubMed: 31145120
DOI: 10.1097/MOL.0000000000000622 -
Audiology Research Sep 2023The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a...
The importance of translational research in the medical sciences is growing logarithmically, as this type of research provides the translation of basic research into a clinical product (a drug, therapeutic agent or means of monitoring a disease), as well as the inverse translation of clinical findings into basic research models [...].
PubMed: 37887844
DOI: 10.3390/audiolres13050063 -
The Journal of Spinal Cord Medicine Nov 2013
Topics: Humans; Spinal Cord Injuries
PubMed: 24351579
DOI: 10.1179/1079026813Z.000000000229 -
Deutsches Arzteblatt International Apr 2009The choice of study type is an important aspect of the design of medical studies. The study design and consequent study type are major determinants of a study's...
BACKGROUND
The choice of study type is an important aspect of the design of medical studies. The study design and consequent study type are major determinants of a study's scientific quality and clinical value.
METHODS
This article describes the structured classification of studies into two types, primary and secondary, as well as a further subclassification of studies of primary type. This is done on the basis of a selective literature search concerning study types in medical research, in addition to the authors' own experience.
RESULTS
Three main areas of medical research can be distinguished by study type: basic (experimental), clinical, and epidemiological research. Furthermore, clinical and epidemiological studies can be further subclassified as either interventional or noninterventional.
CONCLUSIONS
The study type that can best answer the particular research question at hand must be determined not only on a purely scientific basis, but also in view of the available financial resources, staffing, and practical feasibility (organization, medical prerequisites, number of patients, etc.).
Topics: Biomedical Research; Clinical Trials as Topic; Germany; Periodicals as Topic; Research; Science
PubMed: 19547627
DOI: 10.3238/arztebl.2009.0262 -
The Journal of Medical Investigation :... 2020Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein... (Review)
Review
Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.
Topics: Humans; Intracranial Arteriovenous Malformations
PubMed: 33148892
DOI: 10.2152/jmi.67.222 -
Frontiers in Endocrinology 2018Colorectal Cancer (CRC) is one of the most frequently encountered neoplasms in humans. The incidence of CRC has been increasing and new strategies for prevention,... (Review)
Review
Colorectal Cancer (CRC) is one of the most frequently encountered neoplasms in humans. The incidence of CRC has been increasing and new strategies for prevention, including chemoprevention, are required to lower its incidence and associated mortality. Metformin is a biguanide compound commonly used for the treatment of diabetes mellitus. Many recent basic research, epidemiological and clinical trial studies have indicated that metformin has benefits not only in diabetes treatment, but also in lowering the risk of developing cancer (including CRC). These studies indicate that metformin may be a candidate chemoprevention agent for CRC. This review article shall discuss the present evidence of metformin treatment and CRC, as well as outline our challenge in the investigation of metformin use in chemoprevention therapy for colorectal tumors.
PubMed: 30405532
DOI: 10.3389/fendo.2018.00622